ASSEMBLY OF MONOCLONAL-ANTIBODIES WITH IGG1 AND IGA HEAVY-CHAIN DOMAINS IN TRANSGENIC TOBACCO PLANTS

The genes encoding the heavy and light chains of a murine monoclonal a ntibody (mAb Guy's 13) have been cloned and expressed in Nicotiana tab acum. Transgenic plants have been regenerated that secrete full-length Guy's 13 antibody. By manipulation of the heavy chain gene sequence, constant region domains from an immunoglobulin alpha heavy chain have been introduced, and plants secreting Guy's 13 mAb with chimeric gamma /alpha heavy chains have also been produced. For each plant antibody, light and heavy chains have been detected by Western blot analysis and the fidelity of assembly confirmed by demonstrating that the antibody is fully functional, by antigen binding studies. Furthermore, the pla nt antibodies retained the ability to aggregate streptococci, which co nfirms that the bivalent antigen-binding capacity of the full length a ntibodies is intact. The results demonstrate that IgA as well as IgG c lass antibodies can be assembled correctly in tobacco plants and sugge st that transgenic plants may be suitable for high-level expression of more complex genetically engineered immunoglobulin molecules. Since m Ab Guy's 13 prevents streptococcal colonization in humans, transgenic plant technology may have therapeutic applications.